Vector-borne diseases account for more than 17% of all infectious diseases worldwide, with over a billion cases causing more than 1 million deaths annually. According to the World Health Organization, the worldwide incidence of dengue and other arboviruses has risen 30-fold in the past 30 years, and more countries are reporting their first outbreaks of the diseases like Zika, dengue, chikungunya, and yellow fever; putting more than half of the worlds population at risk of contracting these diseases. Vector-borne diseases are comprised of human and animal diseases caused by pathogens (viruses and parasites) which are transmitted by the bite of infected blood-feeding arthropods such as mosquitoes and sand flies. Pathogen transmission occurs when an infected mosquito or sand fly probes the vertebrate hosts skin in search of a blood meal. When attempting to blood-feed, arthropods face both mechanical and pharmacological problems. After cutting or drilling the host skin, blood feeding arthropods trigger the host hemostatic defenses, that constrict blood flow to the injured site. While the blood feeder attempts to modify the bite site to enhance blood feeding success, the hosts ability to react to injury becomes compromised and could facilitate pathogen invasion. Conversely, the vertebrate hosts immune response to these salivary compounds may also affect pathogen transmission. Determining the role of specific salivary molecules in mosquito biology and pathogen transmission is essential, not only to understand the biology of these interactions, but also to develop new control strategies to reduce or eliminate vector-borne diseases. This new gene editing technology opens a wealth of opportunities to advance the field and gain new insights into the biology of vector borne diseases.